The present invention relates to a novel therapeutic use of a known compound, gabapentin, its derivatives, and pharmaceutically acceptable salts. The present invention concerns a method for treating depression in a mammal in need of such treatment.
U.S. Pat. No. 4,024,175 and its divisional 4,087,544 cover the compounds of the instant invention, methods for preparing them, and several uses thereof. The uses disclosed are: protective effect against cramp induced by thiosemicarbazide; protective action against cardiazole cramp; the cerebral diseases epilepsy, faintness attacks, hypokinesia, and cranial traumas; and improvement in cerebral functions. The compounds are useful in geriatric patients. The patents are hereby incorporated by reference.
U.S. Pat. No. 2,948,718 covers carbamazepine, a known anticonvulsant of structural formula ##STR1## Carbamazepine has been reported to have antidepressant activity.
Arch Gen Psychiatry 47 287-8 (1990) discloses the use of progabide as an antidepressant. Progabide is
There is no disclosure in the above references to make obvious the present invention of novel uses of compounds of U.S. Pat. No. 4,024,175 to treat depression.
Depression can be the result of organic disease, secondary to stress associated with personal loss, or idiopathic in origin. There is a strong tendency for familial occurrence of some forms of depression suggesting a mechanistic cause for at least some forms of depression. The diagnosis of depression is made primarily by quantification of alterations in patients' mood. These evaluations of mood are generally performed by a physician or quantified by a neuropsychologist using validated rating scales, such as the Hamilton Depression Rating Scale or the Brief Psychiatric Rating Scale. Numerous other scales have been developed to quantify and measure the degree of mood alterations in patients with depression, such as insomnia, difficulty with concentration, lack of energy, feelings of worthlessness, and guilt. The standards for diagnosis of depression as well as all psychiatric diagnoses are collected in the Diagnostic and Statistical Manual of Mental Disorders (Third Edition Revised) referred to as the DSM-III-R manual published by the American Psychiatric Association, 1987.
GABA is an inhibitory neurotransmitter within the central nervous system. Within the general context of inhibition, it seems likely that GABA-mimetics might decrease or inhibit cerebral function and might therefore slow function and decrease mood leading to depression.
The compound of the instant invention, gabapentin, may produce an anticonvulsant effect through the increase of newly created GABA at the synaptic junction. If gabapentin does indeed increase GABA levels or the effectiveness of GABA at the synaptic junction, then it could be classified as a GABA-mimetic and might decrease or inhibit cerebral function and might therefore slow function and decrease mood leading to depression.
The fact that a GABA agonist or GABA-mimetic, might work just the opposite way by increasing mood and thus, be an antidepressant, is a new concept, different from the prevailing opinion of GABA activity heretofore. Thus, gabapentin has now been found to have an antidepressant action in patients with major and minor forms of depression.